1. Field of the Invention
This invention relates to a method of manufacture of a controlled release solid unit dosage form based on the hydrophilic gel matrix principle for administration of medicaments. Also the solid unit dosage forms are included. Specifically, this invention relates to the use of a waterbased granulating solution containing an additive which inhibits gel formation of hydroxypropyl methylcellulose (HPMC) during granulation but not of the gelling of the final dosage form in vivo, which is necessary for its function.
2. Background and Prior Art
Granulation of hydrophilic gel matrix dosage forms containing HPMC as main gelling agent, has usually been performed with ethanol and methanol (U.S. Pat. No. 4,871,548), isopropanol and aqueous mixtures thereof (EP-A-157695). According to the product information brochure from a manufacturer of this polymer, (DOW 1987, `Formulating for controlled release with METHOCEL cellulose ethers`, page 24-5) aqueous granulation of very finely sized particles can be applied, but it is also pointed out that in doing so, a situation may occur, where the granules obtained are very hard and difficult to grind. This is connected with a high polymer content of the granulate. The proposed way in the brochure to minimize these problems is to granulate with a hydroalcoholic solution and thereby reduce the water content in the system.
Production of such dosage forms has also been performed by water granulation of parts of the composition, exluding the gelling agent. This is described in the above cited EP-A-157695. In other cases direct compression have been used (U.S. Pat No. 4,369,172).